The inflammatory processes are known to be triggered by increased metabolic activity of arachidonic acid. Arachidonic acid diverges down into two main pathways during this process, the cyclooxygenase (COX) and lipoxygenase (LOX) pathways. The COX pathways lead to prostaglandins and thromboxane production and the LOX pathways leads to leukotrienes (LTS) and hydroxyl eicosatetraenoic acid (HETEs). These classes of inflammatory molecules exert profound biological effects, which enhance the development and progression of human cancers. Inhibition of 5-lipoxygenase indirectly reduces the expression of TNF-α. Both 5-Lipoxygenase and TNF-α therefore, are the target enzymes useful for identifying inhibitors, which have the potential to cope with a variety of inflammations and hypersensitivity-based human diseases including asthma, arthritis, bowel diseases such as ulcerative colitis and circulatory disorders such as shock and ischemia.
Asthma is the most common disease of diffuse airway inflammation caused by variety of stimuli and characterized by reversible and recurrent attacks of breathlessness and wheezing. US Census Bureau; Population Estimates and International Data Base, 2004 estimated that globally 373,847,408 people suffer from Asthma. An approximate 30.2 million American citizens have been diagnosed with asthma. Children and teenagers from 5-17 years of age have the highest prevalence rates. In 2004, 14.01% children were diagnosed with asthma.
The pathophysiology of asthma consists of chronic inflammation of airways accompanied by a degree of airway remodeling, which results in decreased airway caliber. Accumulation of inflammatory cells in to the airway lining, together with inflammatory cascade contribute to the development of edema, hyper-secretion of mucus and epithelial cell shedding which results in airway plugging. The elevated IgE levels results in hypersensitivity.
The enriched Boswellia composition used in various exemplary embodiments of the present invention contains a unique blend of triterpenes, selectively enriched with the most active boswellic acid called 3-O-acetyl-11-keto-β-boswellic acid (AKBA) and characterized by a lack of significant quantities of the components present in regular Boswellia serrata extracts except AKBA, which is a minor component in regular extracts and a major component in the enriched Boswellia composition. The components present in regular extracts are 1) β-boswellic acid, 2) 3-O-acetyl-β-boswellic acid, 3) 11-keto-β-boswellic acid, 4) 3-O-acetyl-11-keto-β-boswellic acid. 5) 9-ene-β-boswellic acid, 6) 3α-hydroxyurs-9,11-diene-24-oic acid, 7) 2α,3α-hydroxyurs-12-ene-24-oic acid. The components of the unique Boswellia enriched product used in various exemplary embodiments of the present invention are 1) 3-O-acetyl-11-keto-β-boswellic acid, 2) 3-O-acetyl-9(11)-dehydro-β-boswellic acid, 3) 3-O-acetyl-11-keto-β-amirin, 4) 3-O-acetyl-11-keto-α-boswellic acid. An enriched extract containing more than 30% 3-O-acetyl-11-keto-β-boswellic acid is preferably used in various exemplary embodiments of the present invention. Extracts enriched to higher concentration of AKBA may also be used. A suitable enriched extract may be obtained from Laila Nutraceuticals, India, under the brand name 5-Loxin®.
Aegle marmelos (Bael) is a medium sized tree that grows up to 40 ft. It is native to Central and Southern India, Pakistan, Bangladesh, and Burma. The flesh of the Aegle marmelos fruit is eaten raw or processed into drinks or flavoring. Unripe pulp is used to treat diarrhea and dysentery. All other parts of the plant are used for a wide variety of medicinal purposes. Fruit or leaf or root or bark extracts or mixtures thereof are used in various exemplary embodiments of the present invention.
Zingiber officinale (Ginger) has been used as a treatment for nausea, diarrhea and epigastric and joint pains in Ayurvedic and traditional Chinese medicine. Ginger has antihistaminic activity. Ginger's oleoresin constituents have potent inhibitory effects on the biosynthesis of pro inflammatory prostaglandins and leukotrienes. Shogaol and Paradol inhibit COX-2 activity and Gingerol inhibits 5-LOX enzyme activity. In an uncontrolled trial, all seven arthritis patients treated with half gram of powdered ginger per day reported pain relief and decreased signs of inflammation. Ginger root extracts standardized to 5-15% gingerols are used to prepare this composition. Extracts standardized to other concentrations and other components could also be used for making the present inventive compositions.
Garcinia mangostana L belongs to the Guttiferae family. It is commonly known as Mangosteen. Mangosteen is a slow-growing tropical, evergreen tree and can attain 6-25 m in height with leathery glabrous leaves. The tree is mainly found in India, Myanmar, Sri Lanka and Thailand. The edible fruits of this plant are considered to be one of the best of all tropical fruits. In the ayurvedic system of medicine, the fruit hull of the plant finds wide application, mainly as an anti-inflammatory agent and in the treatment of diarrhea. Garcinia mangostana alcohol extracts or hydroalcohol extracts standardized to α-mangostin are used in various exemplary embodiments of the present invention. However Garcinia mangostana extracts selectively enriched in γ-mangostin may also be used.
Various exemplary embodiments of the present invention provide pharmaceutical or dietary supplement compositions comprising Boswellia serrata extract selectively enriched in 3-O-acetyl-11-keto-β-boswellic acid (AKBA) and extracts of Aegle marmelos for improved therapeutic effect in the prevention, treatment and control of asthma and other inflammatory diseases.
Further exemplary embodiments provide medicinal compositions comprising an effective amount of an enriched Boswellia extract containing from 10% to 99% by weight of 3-0-acetyl-11-keto-β-boswellic acid; and an effective amount of a second extract selected from the group consisting of an extract of Aegle marmelos, an extract of Zingiber officinale, an extract of Garcinia mangostana, and mixtures thereof.
Further embodiments of the invention are directed to methods of ameliorating the effects of adipocyte fatty acid binding protein (aP2) mediated disease conditions by administering an effective amount of a composition including Boswellia serrata extract selectively enriched in 3-O-acetyl-11-keto-β-boswellic acid (5-Loxin), in combination with Aegle marmelos extract, Zingiber officinale, Garcinia mangostana, or mixtures thereof for improved therapeutic effect.
Additional embodiments of the invention are directed to methods of ameliorating the effects of adipocyte fatty acid binding protein (aP2) mediated disease conditions by administering an effective amount of a composition including Boswellia serrata extract selectively enriched in 3-O-acetyl-11-keto-β-boswellic acid (5-Loxin) and Aegle marmelos extract, optionally in combination with Zingiber officinale and/or Garcinia mangostana for improved therapeutic effect.
Still other embodiments of the present invention are directed to methods of ameliorating the effects of 5-Lipoxygenase Activating Protein (FLAP) and Cysteinyl Leukotriene (Cys LT)-1 mediated disease conditions by administering an effective amount of a composition comprising Boswellia serrata extract selectively enriched in 3-O-acetyl-11-keto-β-boswellic acid such as 5-Loxin and extracts of Aegle marmelos, optionally in combination with Zingiber officinale and Garcinia mangostana for improved therapeutic effect.
Further embodiments of the present invention provide efficacious compositions comprising Boswellia extract selectively enriched in AKBA, extracts/fractions/pure isolates selected from Aegle marmelos, and one or more extracts/fractions/pure isolates selected from Zingiber officinale, Garcinia mangostana, optionally in combination with one or more pharmaceutically and nutraceutically acceptable additives or excipients.
Additional embodiments of the present invention provide compositions comprising Boswellia extract selectively enriched in AKBA, extracts/fractions/pure isolates selected from Aegle marmelos, and one or more extracts/fractions/pure isolates selected from Zingiber officinale, Garcinia mangostana, optionally in combination with one or more other known anti-inflammatory or anti-asthma or immune modulating herbs.